Blood Vessel Structure and Function
Blood vessels are dynamic structures that constrict, relax, pulsate, and proliferate. Within the body, blood vessels form a closed delivery system that begins and ends at the heart. There are three major types of blood vessels: (i) arteries; (ii) capillaries and (iii) veins. As the heart contracts, it forces blood into the large arteries leaving the ventricles. Blood then moves into smaller arteries successively, until finally reaching the smallest branches, the arterioles, which feed into the capillary beds of organs and tissues. Blood drains from the capillaries into venules, the smallest veins, and then into larger veins that merge and ultimately empty into the heart.
Arteries carry blood away from the heart and “branch” as they form smaller and smaller divisions. Arterial walls consist of three layers: an intima (innermost layer); a media (middle muscular layer); and an adventitia (outermost layer) (Park K-W et al. J. Korean Neurosurg. Soc. 2008; 44(3): 109-115). In contrast, veins carry blood toward the heart and “merge” into larger and larger vessels approaching the heart. In the systemic circulation, arteries carry oxygenated blood and veins carry oxygen-poor blood. In the pulmonary circulation, the opposite is true. The arteries (still defined as the vessels leading away from the heart), carry oxygen-poor blood to the lungs, and the veins carry oxygen-rich blood from the lungs to the heart.
The only blood vessels that have intimate contact with tissue cells in the human body are capillaries. In this way, capillaries help serve cellular needs. Exchanges between the blood and tissue cells occur primarily through the thin capillary walls.
The walls of most blood vessels (the exception being the smallest vessels, e.g., venules), have three layers, or tunics, that surround a central blood-containing space called the vessel lumen.
The innermost tunic (layer) is the tunica intima. The tunica intima contains the endothelium, the simple squamous epithelium that lines the lumen of all vessels. The endothelium is continuous with the endocardial lining of the heart, and its flat cells fit closely together, forming a slippery surface that minimizes friction so blood moves smoothly through the lumen. In vessels larger than 1 mm in diameter, a sub-endothelial layer, consisting of a basement membrane and loose connective tissue, supports the endothelium.
The middle tunic (layer), the tunica media, contains mostly circularly arranged smooth muscle cells and sheets of elastin. The activity of the smooth muscle is regulated by sympathetic vasomotor nerve fibers of the autonomic nervous system. Depending on the body's needs at any given time, regulation causes either vasoconstriction (lumen diameter decreases) or vasodilation (lumen diameter increases). The activities of the tunica media are critical in regulating the circulatory system, because small changes in vessel diameter greatly influence blood flow and blood pressure. Generally, the tunica media is the bulkiest layer in arteries, which bear the chief responsibility for maintaining blood pressure and proper circulation.
The outer layer of a blood vessel wall, the tunica externa, is primarily composed of collagen fibers that protect, reinforce and anchor the vessel to surrounding structures. The tunica externa contains nerve fibers, lymphatic vessels, and elastic fibers (e.g., in large veins). In large vessels, the tunica externa contains a structure known as the vasa vasorum, which literally means “vessels of vessels”. The vasa vasorum nourishes external tissues of the blood vessel wall. Interior layers of blood vessels receive nutrients directly from blood in the lumen (See, e.g., The Cardiovascular System at a Glance, 4th Edition, Philip I. Aaronson, Jeremy P. T. Ward, Michelle J. Connolly, November 2012, © 2012, Wiley-Blackwell, Hoboken, N.J.).
Brain Circulation/Cerebral Arteries
FIGS. 1 and 2 are schematic illustrations of the brain's blood vessels. Each cerebral hemisphere is supplied by an internal carotid artery, which arises from a common carotid artery beneath the angle of the jaw, enters the cranium through the carotid foramen, traverses the cavernosus sinus (giving off the ophthalmic artery), penetrates the dura and divides into the anterior and middle cerebral arteries. The large surface branches of the anterior cerebral artery supply the cortex and white matter of the inferior frontal lobe, the medial surface of the frontal and parietal lobes and the anterior corpus callosum. Smaller penetrating branches supply the deeper cerebrum and diencephalon, including limbic structures, the head of the caudate, and the anterior limb of the internal capsule. The large surface branches of the middle cerebral artery supply most of the cortex and white matter of the hemisphere's convexity, including the frontal, parietal, temporal and occipital lobes, and the insula. Smaller penetrating branches supply the deep white matter and diencephalic structures such as the posterior limb of the internal capsule, the putamen, the outer globus pallidus, and the body of the caudate. After the internal carotid artery emerges from the cavernous sinus, it also gives off the anterior choroidal artery, which supplies the anterior hippocampus and, at a caudal level, the posterior limb of the internal capsule. Each vertebral artery arises from a subclavian artery, enters the cranium through the foramen magnum, and gives off an anterior spinal artery and a posterior inferior cerebellar artery. The vertebral arteries join at the junction of the pons and the medulla to form the basilar artery, which at the level of the pons gives off the anterior inferior cerebellar artery and the internal auditory artery, and, at the midbrain, the superior cerebellar artery. The basilar artery then divides into the two posterior cerebral arteries. The large surface branches of the posterior cerebral arteries supply the inferior temporal and medial occipital lobes and the posterior corpus callosum; the smaller penetrating branches of these arteries supply diencephalic structures, including the thalamus and the subthalamic nuclei, as well as part of the midbrain (see Principles of Neural Sciences, 2d Ed., Eric R. Kandel and James H. Schwartz, Elsevier Science Publishing Co., Inc., New York, pp. 854-56 (1985)).
Interconnections between blood vessels (anastomoses) protect the brain when part of its vascular supply is compromised. At the circle of Willis, the two anterior cerebral arteries are connected by the anterior communicating artery and the posterior cerebral arteries are connected to the internal carotid arteries by the posterior communicating arteries. Other important anastomoses include connections between the ophthalmic artery and branches of the external carotid artery through the orbit, and connections at the brain surface between branches of the middle, anterior, and posterior cerebral arteries (Principles of Neural Sciences, 2d Ed., Eric R. Kandel and James H. Schwartz, Elsevier Science Publishing Co., Inc., New York, pp. 8556 (1985)).
The circle of Willis at the base of the brain is the principal arterial anastomotic trunk of the brain. Blood reaches it mainly via the vertebral and internal carotid arteries. Anastomoses (interconnections between blood vessels) occur between arterial branches of the circle of Willis over the cerebral hemispheres and via extracranial arteries that penetrate the skull through various foramina.
The circle of Willis is formed by anastamoses between the internal carotid, basilar, anterior cerebral, anterior communicating, posterior cerebral, and posterior communicating arteries. The internal carotid artery terminates in the anterior cerebral and middle cerebral arteries. Near its termination, the internal carotid artery gives rise to the posterior communicating artery, which joins caudally with the posterior cerebral artery. The anterior cerebral arteries connect via the anterior communicating artery.
The lateral surface of each cerebral hemisphere is supplied mainly by the middle cerebral artery. The medial and inferior surfaces of the cerebral hemispheres are supplied by the anterior cerebral and posterior cerebral arteries.
The middle cerebral artery, a terminal branch of the internal carotid artery, enters the lateral cerebral fissure and divides into cortical branches that supply the adjacent frontal, temporal, parietal and occipital lobes. Small penetrating arteries, the lenticulostriate arteries, arise from the basal portion of the middle cerebral artery to supply the internal capsule and adjacent structures.
The anterior cerebral artery extends medially from its origin from the internal carotid artery into the longitudinal cerebral fissure to the genu of the corpus callosum, where it turns posteriorly close to the corpus callosum. It gives branches to the medial frontal and parietal lobes and to the adjacent cortex along the medial surface of these lobes.
The posterior cerebral artery arises from the basilar artery at its rostral end usually at the level of the midbrain, curves dorsally around the cerebral peduncle, and sends branches to the medial and inferior surfaces of the temporal lobe and to the medial occipital lobe. Branches include the calcarine artery and perforating branches to the posterior thalamus and subthalamus.
The basilar artery is formed by the junction of the vertebral arteries. It supplies the upper brain stem via short paramedian, short circumferential, and long circumferential branches.
The midbrain is supplied by the basilar, posterior cerebral, and superior cerebellar arteries. The pons is supplied by the basilar, anterior cerebellar, inferior cerebellar, and superior cerebellar arteries. The medulla oblongata is supplied by the vertebral, anterior spinal, posterior spinal, posterior inferior cerebellar, and basilar arteries. The cerebellum is supplied by the cerebellar arteries (superior cerebellar, anterior inferior cerebellar, and posterior inferior cerebellar arteries).
The choroid plexuses of the third and lateral ventricles are supplied by branches of the internal carotid and posterior cerebral arteries. The choroid plexus of the fourth ventricle is supplied by the posterior inferior cerebellar arteries.
Femoral Artery
The femoral artery is the main artery that provides oxygenated blood to the tissues of the leg. It passes through the deep tissues of the femoral (or thigh) region of the leg parallel to the femur.
The common femoral artery is the largest artery found in the femoral (thigh) region of the body. It begins as a continuation of the external iliac artery at the inguinal ligament which serves as the dividing line between the pelvis and the leg. From the inguinal ligament, the femoral artery follows the medial side of the head and neck of the femur inferiorly and laterally before splitting into the deep femoral artery and the superficial femoral artery.
The superficial femoral artery flexes to follow the femur inferiorly and medially. At its distal end, it flexes again and descends posterior to the femur before forming the popliteal artery of the posterior knee and continuing on into the lower leg and foot. Several smaller arteries branch off from the superficial femoral artery to provide blood to the skin and superficial muscles of the thigh.
The deep femoral artery follows the same path as the superficial branch, but follows a deeper path through the tissues of the thigh, closer to the femur. It branches off into the lateral and medial circumflex arteries and the perforating arteries that wrap around the femur and deliver blood to the femur and deep muscles of the thigh. Unlike the superficial femoral artery, none of the branches of the deep femoral artery continue into the lower leg or foot.
Like most blood vessels, the femoral artery is made of several distinct tissue layers that help it to deliver blood to the tissues of the leg. The innermost layer, known as the endothelium or tunica intima, is made of thin, simple squamous epithelium that holds the blood inside the hollow lumen of the blood vessel and prevents platelets from sticking to the surface and forming blood clots. Surrounding the tunica intima is a thicker middle layer of connective tissues known as the tunica media. The tunica media contains many elastic and collagen fibers that give the femoral artery its strength and elasticity to withstand the force of blood pressure inside the vessel. Visceral muscle in the tunica media may contract or relax to help regulate the amount of blood flow. Finally, the tunica externa is the outermost layer of the femoral artery that contains many collagen fibers to reinforce the artery and anchor it to the surrounding tissues so that it remains stationary.
The femoral artery is classified as an elastic artery, meaning that it contains many elastic fibers that allow it to stretch in response to blood pressure. Every contraction of the heart causes a sudden increase in the blood pressure in the femoral artery, and the artery wall expands to accommodate the blood. This property allows the femoral artery to be used to detect a person's pulse through the skin (See, e.g., The Cardiovascular System at a Glance, 4th Edition, Philip I. Aaronson, Jeremy P. T. Ward, Michelle J. Connolly, November 2012, © 2012, Wiley-Blackwell, Hoboken, N.J.).
Use of the Femoral Artery for Endovascular Procedures
Endovascular diagnostic and therapeutic procedures are generally performed through the femoral artery. Some of the reasons for this generalized approach include its location, easy approach for puncture and hemostasis, low rate of complications, technical ease, wide applicability and relative patient comfort (Alvarez-Tostado J. A. et al. Journal of Vascular Surgery 2009; 49(2): 378-385). Femoral puncture also allows access to virtually all of the arterial territories and affords favorable ergonomics for the operator in most instances (Alvarez-Tostado J. A. et al. Journal of Vascular Surgery 2009; 49(2): 378-385).
Brachial Artery
The brachial artery is a major blood vessel located in the upper arm and is the main supplier of blood to the arm and hand. It continues from the axillary artery at the shoulder and travels down the underside of the arm. Along with the medial cubital vein and bicep tendon, it forms the cubital fossa, a triangular pit on the inside of the elbow. Below the cubital fossa, the brachial artery divides into two arteries running down the forearm: the ulnar and the radial; the two main branches of the brachial artery. Other branches of the brachial artery include the inferior ulnar collateral, profunda brachii, and superior ulnar arteries (See, e.g., The Cardiovascular System at a Glance, 4th Edition, Philip I. Aaronson, Jeremy P. T. Ward, Michelle J. Connolly, November 2012, © 2012, Wiley-Blackwell, Hoboken, N.J.).
Use of the Brachial Artery for Endovascular Procedures
Brachial artery access is a critical component of complex endovascular procedures, especially in instances where femoral access is difficult or contraindicated, such as the absence of palpable femoral pulses, severe common femoral occlusive disease, recent femoral intervention or surgery or femoral aneurysms/pseudoaneurysms. It is a straightforward procedure with a high success rate for percutaneous cannulation (Alvarez-Tostado J. A. et al. Journal of Vascular Surgery 2009; 49(2): 378-385). However, there is a general reluctance to puncture the right brachial artery due to the need to navigate through the innominate artery and arch and due to the risk for complications such as direct nerve trauma and ischemic occlusion resulting in long-term disability (Alvarez-Tostado J. A. et al. Journal of Vascular Surgery 2009; 49(2): 378-385; Cousins T. R. and O'Donnell J. M. AANA Journal 2004; 72(4): 267-271).
Cerebral/Intracranial Aneurysms
An aneurysm in the brain (i.e., cerebral or intracranial aneurysm) is a weak area in the wall of a cerebral blood vessel that causes the blood vessel to bulge or balloon out. Aneurysms typically develop during adulthood and rupture risk increases with age. Subarachnoid hemorrhage (SAH) is the most serious presentation of ruptured intracranial aneurysms (Seibert B et al. Frontiers in Neurology 2011; 2(45): 1-11). The mean age for aneurysmal SAH is about 50 years (Phillips L H et al. Neurology 1980; 30, 1034-1040). Estimated annual incidence rates of SAH range from 10 to 15 cases per 100,000; roughly 30,000 cases of SAH in the United States each year. Two-thirds of patients with aneurysm rupture either die or have a disabling neurological deficit (Stapf C and Mohr J P (2004) “Aneurysms and subarachnoid hemorrhage—epidemiology,” in Management of Cerebral Aneurysms, eds. LeRoux P D, Winn H R, Newell D W, editors. (Philadelphia: Saunders), 183-187). More specifically, ruptured aneurysms account for approximately 85% of non-traumatic SAH and are associated with a 30-day mortality rate of 45% and a morbidity rate of 25% (van Gijn J et al. Lancet 2007; 369 (9558): 306-318).
Typical locations at risk for the development of aneurysms are vessel branching points, where structural irregularities in the collagen matrix exist, and elevated hemodynamic stresses due to segments involving short radii of curvature are more observed (Meng H et al. Stroke 2007; 38(6): 1924-1931; Finlay H M et al. Stroke 1998; 29(8): 1595-1601; Rowe A J et al. J. Vasc. Res. 2003; 40(4): 406-415). Studies have shown that abnormal hemodynamic stress plays an important role in aneurysm formation and growth (Meng H et al. Stroke 2007; 38(6): 1924-1931).
Classification of Cerebral/Intracranial Aneurysms
Several schemes are used to classify intracranial aneurysms; the most obvious being ruptured lesions versus unruptured lesions (Seibert B et al. Frontiers in Neurology 2011; 2(45): 1-11). With respect to morphology, aneurysms are classified as saccular (rounded shape) or non-saccular. Non-saccular intracranial aneurysms such as fusiform (spindle-shaped), dolichoectatic (widening of a segment of an artery around the entire blood vessel), and dissecting aneurysms (artery wall rips longitudinally) are rare with an incidence of less than 0.1% (Anson J A et al. J. Neurosurg. 1996; 84(2): 185-193). Intracranial aneurysms also are classified by aneurysm location. The predominant location for saccular aneurysms is the anterior circulation (about 90%), with most arising from the circle of Willis (Bonneville F et al. Neuroimaging Clin. N. Am. 2006; 16(3): 371-382). The anterior communicating complex is the most common location (roughly 30-35%), followed by the internal carotid artery (roughly 30%). The basilar apex represents the most common location in the posterior circulation and accounts for about 10% of all intracranial aneurysms (Bonneville F et al. Neuroimaging Clin. N. Am. 2006; 16(3): 371-382). Aneurysms are also classified by size. Size classification subgroups include small (<10 mm), large (10-25 mm), and giant (>25 mm) in diameter. According to Wiebers et al., aneurysms smaller than 12 mm in dome size account for more than 75% of unruptured aneurysms (Wiebers D O et al. Lancet 2003; 362(9378): 103-110). The establishment of endovascular therapy has led to further classification of aneurysms based on the size of the aneurysmal neck (Seibert B et al. Frontiers in Neurology 2011; 2(45): 1-11).
Pathophysiology of Cerebral/Intracranial Aneurysms
Formation of an intracranial aneurysm is thought to be a consequence of a systemic vascular pathology, which is associated with pleomorphisms in different candidate genes (Krex D et al. Acta Neurochir. (Wien) 2001; 143(5): 429-448; Yurt A et al. J. Clin. Neurosci. 2010; 17(9): 1119-1121). A higher prevalence of aneurysms in the cerebrovascular system may also be attributed to alterations in hemodynamic and histological features (Stehbens W E et al. Neurol. Res. 1990; 12(1): 29-34; Kondo S et al. Stroke 1997; 28(2): 398-403; Rowe A J et al. J. Vasc. Res. 2003; 40(4): 406-415; Shojima M et al. Stroke 2004; 35(11): 2500-2505). Cerebral arteries are particularly susceptible to aneurysm formation due to the absence of an external elastic lamina (tissue that forms the outermost part of the tunica intima), lack of supportive perivascular tissues, attenuated tunica media, and irregularities near bifurcations (Stehbens W E et al. Neurol. Res. 1990; 12(1): 29-34; Rowe A J et al. J. Vasc. Res. 2003; 40(4): 406-415). The internal elastic lamina is an important layer of the arterial wall, especially in cerebral vessels. Disruption of this layer would promote formation of aneurysms (Yong-Zhong G and van Alphen H A Neurol. Res. 1990; 12(4): 249-255). Particularly, the regions around the bifurcations have atypical wall structures with a discontinuity of the muscle cells of the tunica media as a medial defect in connection with a predominance of collagen fibers over elastic fibers (Rowe A J et al. J. Vasc. Res. 2003; 40(4): 406-415; Seibert B et al. Frontiers in Neurology 2011; 2(45): 1-11). In addition to these atypical wall structures, non-uniform collagen framework in the bifurcation region of brain arteries may further induce development of intracranial aneurysms (Rowe A J et al. J. Vasc. Res. 2003; 40(4): 406-415).
Several studies have demonstrated that arterial blood flow disturbance and hypertension in the brain vessels lead to increased hemodynamic stress on arterial walls. Some studies also present strong association between wall shear stress (WSS) and initiation of cerebral aneurysm formation in experimental models (Kondo S. et al. Stroke 1997; 28(2): 398-403; Shojima M et al. Stroke 2004; 35(11): 2500-2505). A prolonged high WSS induces matrix metalloproteinase production and fragmentation of the internal elastic lamina at, or immediately adjacent to, the apex of vessel bifurcations (Masuda H et al. Arterioscler. Thromb. Vasc. Biol. 1999: 19(10): 2298-2307; Shojima M et al. Stroke 2004; 35(11): 2500-2505; Meng H et al. Stroke 2007; 38(6): 1924-1931). Prolonged elevation of blood pressure leads to excessive mechanical loading and causes remodeling of the arterial wall. The exact mechanisms involved in the tissue remodeling are not completely understood, but decreased structural integrity of the tissue may be one of the underlying factors contributing to aneurysm formation and growth (Seibert B et al. Frontiers in Neurology 2011; 2(45): 1-11).
Types of Cerebral/Intracranial Aneurysms
Saccular Intracranial Aneurysms
Saccular intracranial aneurysms, which account for 90% of intracranial aneurysms, are a result of aberrations to the normal arterial structure, which consists of the tunica intima (adjacent to the lumen of the vessel), the tunica media (the muscular middle layer), and the tunica adventitia (the outer layer composed mainly of connective tissue) (Keedy A Mcgill J. Med. 2006; 9(2): 141-146). Saccular aneurysms occur when there is collagen deficiency in the internal elastic lamina and breakdown of the tunica media. An outpouching, consisting of only tunica intima and adventitia, protrudes through the defect in the internal elastic lamina and tunica media to produce the aneurysmal sac (Austin G et al. Ann. Clin. Lab. Sci. 1993; 23(2): 97-105; Stehbens W E et al. Surg. Neurol. 1989; 31(3): 200-202). The impaired integrity of the wall may be due to congenital weakness or absence of the tunica media or adventitia, degenerative alterations of the internal elastic lamina (from hypertension, turbulent flow, or atherosclerotic deposits in the wall), or both (Gasparotti R et al. Eur. Radiol. 2005; 15(3): 441-447). Low collagen and elevated plasma elastase have been observed in patients with aneurysms, suggesting that vascular remodeling involving collagen and elastin plays a role saccular intracranial aneurysm formation (Wagner M and Stenger K Crit. Care Nurs. Q. 2005; 28(4): 341-354).
Fusiform Intracranial Aneurysms
Fusiform aneurysms are nonsaccular dilatations involving the entire vessel wall for a short distance, exhibiting a spindle shape when viewed externally (Al-Yamany M and Ross I B Br. J. Neurosurg. 1998; 12(6):572-57; Ceylan S et al. Neurosurg. Rev. 1998; 21(2-3):189-193; Day A L et al. J. Neurosurg. 2003; 99(2):228-240; Findlay J M et al. Can. J. Neurol. Sci. 2002; 29(1): 41-48; Nakayama Y et al. Surg. Neurol. 1999; 51(2): 140-145). This type of aneurysm may be caused by dissection or atherosclerosis, by disorders of collagen and elastin metabolism, by infections and, although rare, by neoplastic invasion of the arterial wall (Ceylan S et al. Neurosurg. Rev. 1998; 21(2-3):189-193; Day A L et al. J. Neurosurg. 2003; 99(2):228-240; Otawara Y et al. Neurosurg. Rev. 1997; 20(2):145-148; Selviaridis P et al. Acta Neurochir (Wien) 2002; 144(3): 295-299). Fusiform aneurysms have different underlying pathologies, hemodynamics, anatomical distributions, natural histories and treatments than do the saccular variety (Day A L et al. J. Neurosurg. 2003; 99(2):228-240). Intracranial fusiform aneurysms are rare, although the number of cases has increased in recent years. They represent approximately 3%-13% of all intracranial aneurysms and are usually located in the vertebrobasilar system (Al-Yamany M and Ross I B Br. J. Neurosurg. 1998; 12(6):572-57; Drake C G and Peerless S J J. Neurosurg. 1997; 87(2); 141-162; Findlay J M et al. Can. J. Neurol. Sci. 2002; 29(1): 41-48).
Intracranial Vertebral Artery Dissecting Aneurysms
Intracranial vertebral artery dissecting (VAD) aneurysms result from a tear in the wall of an artery leading to the intrusion of blood within the layers of the arterial wall, more specifically, from a tear in the wall of a major artery leading to the intrusion of blood (intramural hematoma) between the media and the adventitia (Park K-W et al. J. Korean Neurosurg. Soc. 2008; 44(3): 109-115; Thanvi B et al. Postgrad. Med. J. 2005; 81(956): 383-388). The overall incidence of VAD is approximately 1-1.5 per 100,000 (Park K-W et al. J. Korean Neurosurg. Soc. 2008; 44(3): 109-115). Spontaneous dissections of the carotid and vertebral artery account for only about 2 percent of ischemic strokes, but they are a major cause of ischemic stroke in young and middle-aged patients (roughly 10% to 25%) (Bassetti C et al. Stroke 1996; 27(10): 1804-1807; Giroud M et al. J. Neurol. Neurosurg. Psychiatry 1994; 57(11): 1443; Schievink W I Curr. Opin. Cardiol. 2000; 15(5): 316-321; Schievink W I et al. Neruology 1994; 330(6): 393-397). Spontaneous dissections of the vertebral arteries affect all age groups, including children, but there is a distinct peak in the fifth decade of life (Bassetti C et al. Stroke 1996; 27(10): 1804-1807; Schievink W I et al. Neurology 1994; 330(6): 393-397; Schievink W I et al. Neurology 1994; 44(9): 1607-1612).
Patients with a spontaneous dissection of the vertebral artery are thought to have an underlying structural defect of the arterial wall (Park K-W et al. J. Korean Neurosurg. Soc. 2008; 44(3): 109-115; Schievink W I N. Eng. J. Med. 2001; 344(12): 898-906). Heritable connective tissue disorders, such as Ehlers-Danlos syndrome type IV, Marfan's syndrome, autosomal dominant polycystic kidney disease, and osteogenesis imperfecta type I, are believed to be associated with an increased risk of spontaneous dissections of the vertebral arteries (Schievink W I et al. Stroke 1994; 25(12): 2492-2496; Schievink W I et al. Stroke 1994; 25(4): 889-903).
Mycotic Intracranial Aneurysms
Cerebral mycotic aneurysms (CMAs) or infectious intracranial aneurysms represent less than 5% of all intracerebral aneurysms (Kannoth S et al. J. Neurolog. Sci. 2007; 256: 3-9). CMAs are most commonly seen in patients with septicemia and HIV/AIDS and are a particularly well-known complication of infective endocarditis (IE). Intravenous drug abuse and “relative immunocompromised” states such as diabetes are becoming more commonly associated with CMAs (Corr P et al. Am. J. Neuroradiol. 1995; 16: 745-48; Peters P J et al. Lancet Infect. Dis. 2006; 6: 742-748; Lee W K et al. Radiographics 2008; 28: 1853-1868). Studies have shown that between 1%-10% of patients with IE have CMAs; and of patients with CMAs, approximately 65% have IE (Peters P J et al. Lancet Infect. Dis. 2006; 6: 742-748; Ducruet A F et al. Neurosurg. Rev. 2010; 33: 37-46). In “strongly immunocompromised” patients, CMAs are prone to more rapid growth and rupture (Hurst R W et al. Am. J. Neuroradiol. 2001; 22: 858-863; Horten B C et al. Arch. Neurol. 1976; 33: 577-579; Minnerup J et al. Neurology 2008; 71: 1745). If there is direct meningeal extension of infection, CMAs are often located more proximally than their usual location at distal branch points. In addition, CMAs from atypical infections, especially fungal infections, are particularly lethal (Hurst R W et al. Am. J. Neuroradiol. 2001; 22: 858-863; Horten B C et al. Arch. Neurol. 1976; 33: 577-579; Minnerup J et al. Neurology 2008; 71: 1745).
Cavernous Carotid Aneurysms (CCAs)
Cavernous carotid aneurysms (CCAs) are considered benign lesions of the cavernous internal carotid artery which are most often asymptomatic (Eddleman C S et al. Neurosurgical Focus 2009; 26(5): E4). These aneurysms, especially when small, rarely rupture and thus have a low risk of causing major morbidity and mortality (Eddleman C S et al. Neurosurgical Focus 2009; 26(5): E4; Kupersmith M J et al. J Stroke Cerebrovasc Dis 2002; 11:9-14; Stiebel-Kalish H, et al. Neurosurgery 2005; 57:850-57; Wiebers D. Lancet 2003; 362:103-10). Larger CCAs (>13 mm) have a 5-year rupture rate of 9.4% (Wiebers D. Lancet 2003; 362:103-10). When they do rupture, CCAs typically rupture into the cavernous sinus, which leads to carotid cavernous fistula formation (a short-circuiting of the arterial blood into the venous system of the cavernous sinuses; See Karaman E et al. J. Craniofac. Surg. 2009; 20(2); 556-558); a far less catastrophic event than rupture of intradural aneurysms (Tanweer O et al. Am. J. Neuroradiol. 2014; 35: 2334-2340). However, although rare, once CCAs reach the size at which they penetrate or protrude through the dura, they carry the risk of subarachnoid hemorrhage (SAH) (Eddleman C S et al. Neurosurgical Focus 2009; 26(5): E4; Tanweer O et al. Am. J. Neuroradiol. 2014; 35: 2334-2340).
Treatment of Aneurysms
Surgical Clipping
Surgical clipping of an intracranial aneurysm, which involves the application of a silver clip across the neck of the aneurysm, has the advantage of being a time-honored, durable and versatile method for treating most intracranial aneurysms (Seibert B et al. Front. Neruol. 2011; 2(45): 1-11). It is rare for an intracranial aneurysm to recur once it has been properly clipped, and there are very few aneurysms that are not amenable to some surgical repair technique (Campi A et al. Stroke 2007; 38(5): 1538-1544; Tsutsumi K et al. Stroke 2001; 32(5): 1191-1194).
However, surgical repair of intracranial aneurysms does have several disadvantages; including that it requires an open operation and physical manipulation of the brain (Mason A M et al. J. Korean Neurosurg. Soc. 2009; 45(3): 133-142). A number of characteristics of either the patient and/or the aneurysm can make them undesirable for surgical management as well, including aneurysms in elderly patients, patients in very poor medical condition or who present with cerebral vasospasm, patients who have multiple aneurysms or aneurysms that have calcified necks or unfavorable surgical anatomy (e.g., fusiform aneurysms, blister-like aneurysms, wide-neck aneurysms, thrombotic aneurysms, giant aneurysms, aneurysms <3 mm in size, etc.) (Mason A M et al. J. Korean Neurosurg. Soc. 2009; 45(3): 133-142).
Endovascular Coiling
Endovascular coiling is a minimally invasive technique performed to prevent blood from flowing into an aneurysm. During endovascular coiling, a catheter is passed through the groin up to the artery containing the aneurysm. A microcatheter with a coil attached is inserted through the initial catheter. When the microcatheter has reached and been inserted into the aneurysm, an electrical current is used to separate the coil from the catheter. The coil is permanently left to seal off the opening of the aneurysm. Depending on the size of the aneurysm, more than one coil may be needed to completely seal off the aneurysm. The coil induces embolization (clotting) of the aneurysm, which prevents blood from flowing into the aneurysm, which in turn, prevents subarachnoid hemorrhage (Seibert B et al. Frontiers in Neurology 2011; 2(45): 1-11).
While endovascular coiling of intracranial aneurysms has offered an alternative treatment option to open surgery (i.e., surgical clipping), there are serious risks to consider. Some of these risks overlap with those seen in surgical clipping and others are unique to endovascular therapy. Procedural complications include thromboembolism, cerebral embolization, aneurysm perforation, parent artery occlusion, coil migration, arterial dissection, and vasospasm (Murayama Y et al. J. Neurosurg. 2003; 98(5): 959-966; Gonzalez N et al. Am. J. Neuroradiol. 2004; 25(4): 577-583).
Stent-Assisted Coiling
Stent-assisted coiling has improved the ability to treat difficult and complicated aneurysms. However, while these devices provide another treatment option for endovascular repair, additional risks are associated with stent placement compared to coiling alone (Seibert B et al. Frontiers in Neurology 2011; 2(45): 1-11). Placing a stent in the parent artery requires lifetime use of anti-platelet agents to reduce the risk of thrombosis based stenosis within the stent (Kanaan H et al. Neurosurgery 2010; 67(6): 1523-1532). The need for anti-platelet therapy limits the role of stent placement in patients with ruptured aneurysms. These patients may need additional invasive procedures such as ventriculostomy, decompressive craniectomy, tracheostomy, or gastrostomy (Seibert B et al. Frontiers in Neurology 2011; 2(45): 1-11). The risk of these procedures is increased due to anti-platelet or anticoagulation therapy (Mocco J et al. J. Neurosurg. 2009; 110(1): 35-39).
Flow Diversion
The primary goal of a flow diversion device is to divert flow away from the aneurysm by placing a mesh stent or a structure similar to a stent, on the aneurysm neck along the parent artery. By decoupling blood flow between the parent artery and aneurysmal sack, a flow diverter can create blood stasis to allow for thrombus formation inside the aneurysm. In terms of design, flow diversion devices consist of a highly flexible tubular structure with a mesh. The porosity of the mesh is less than that of typical stents (Seibert B et al. Frontiers in Neurology 2011; 2(45): 1-11).
These devices are typically deployed in situations where established techniques, such as coiling and stent-assisted coiling, are not viable options. However, increased technical complications with deployment of flow diverters have been reported. In one study, an overall complication rate of 38%, including parent artery stenosis, distal embolism, in-device thrombosis, branch occlusion, and hemorrhage or mass effects was reported (Lubicz B et al. Stroke 2010; 41(10): 2247-2253). In another study, parent artery occlusion was seen in seven (14%) patients, with additional arterial narrowing in three (6%) patients (Byrne J et al. Plos ONE 2010; 2; 5(9). pii: e12492. Doi: 10.1371/journal.pone.0012492).
In addition, clinicians must use caution in deployment of flow diverters when aneurysms are located near regions of side branching arteries. Incorrect placement could prevent blood flow to an otherwise healthy artery. Another concern with flow diverters is that the low porosity (i.e., small open spaces in the mesh) needed to reduce blood flow, will be problematic if additional coiling is needed after deployment. Anti-coagulants required for flow diverters may be beneficial for prevention of in-device thrombus, but could negatively impact the time for thrombus formation inside the aneurysm without the additional coil packing used with stents. The interaction of thrombus formation inside aneurysms is not clearly understood. It has been suggested that such thrombus formation could lead to rupture after deployment of a flow diverter (Kulcsar Z et al. Am. J. Neuroadiol. 2011; 32(1): 20-25).
A common complication of endovascular aneurysm repair is the occurrence of an endoleak (persistent blood within the aneurysmal sac following a flow diversion and/or covered stent procedure), which is found in 30-40% of patients intraoperatively (detected by on-table angiogram after flow-diverter and/or peripheral covered stent deployment) and 20-40% of patients during a follow-up examination. Some endoleaks are unavoidable due to the presence of pre-existing patent branch vessels arising from the aneurysm sac, while others occur as a result of poor patient/flow-diverter/covered stent selection. In the latter group, some regions of the stent are poorly apposed to the vessel wall after deployment of the device, allowing “leakage” of a stream of blood between the device and the vessel wall, which continues to fill the aneurysm and/or fistula.
Carotid-Cavernous Fistulas (CCF)
A carotid cavernous fistula (CCF) results from an abnormal communication between the arterial and venous systems within the cavernous sinus in the skull. As arterial blood under high pressure enters the cavernous sinus, the normal venous return to the cavernous sinus is impeded. This causes engorgement of the draining veins, manifesting most dramatically as a sudden engorgement and redness of the eye of the same side. A CCF may form following closed or penetrating head trauma, surgical damage, rupture of an intracavernous aneurysm or in association with connective tissue disorders, vascular diseases and dural fistulas.
Classification of CCFs
Various classifications have been proposed for CCF. For example, CCFs may be divided into low-flow or high-flow, traumatic or spontaneous, and direct or indirect. A traumatic CCF typically occurs after a basal skull fracture. A spontaneous dural cavernous fistula, which is more common, usually results from a degenerative process in older patients with systemic hypertension and atherosclerosis. Direct fistulas occur when the internal carotid artery (ICA) fistulizes into the cavernous sinus whereas indirect fistulas occur when a branch of the ICA or external carotid artery (ECA) communicates with the cavernous sinus.
Table 1 shows one classification system that divides CCF into four varieties based on the type of arterial supply.
TABLE 1CCF classification based on arterial blood supply.ClassificationTypeClassification DescriptionAFistulous supply from the internal carotid arteryBSupply from the dural branches of internal carotid artery (ICA)CSupply from meningeal branches of external carotid artery (ECA)DCombined supply from ICA and ECA
Symptoms of CCF
CCF symptoms include pain, bruit (a humming sound within the skull due to high blood flow through the arteriovenous fistula), progressive visual loss, and pulsatile or progressive proptosis (bulging of the eye anteriorly out of the orbit).
Diagnosis of CCF
Diagnosis is based on magnetic resonance imaging (MRI) scan, magnetic resonance angiography and computerized tomography (CT) scan. A cerebral digital subtraction angiography (DSA) enhances visualization of the fistula. CT scans classically show an enlarged superior ophthalmic vein, cavernous sinus enlargement ipsilateral (on the same side) to the abnormality, and possibly diffuse enlargement of all the extraocular muscles resulting from venous engorgement. Selective arteriography is used to evaluate arteriovenous fistulas.
Treatment of CCF
Endovascular therapy is the mainstay of treatment for CCF. This may be trans-arterial (mostly in the case of direct CCF) or trans-venous (most commonly in indirect CCF). Occasionally, more direct approaches, such as direct trans-orbital puncture of the cavernous sinus or cannulation of the draining superior orbital vein are used when conventional approaches are not possible. Spontaneous resolution of indirect fistulae has been reported but is uncommon. Staged manual compression of the ipsilateral carotid has been reported to assist with spontaneous closure in selected cases.
Direct CCFs may be treated by occlusion of the affected cavernous sinus (with coils, balloon, liquid agents, etc.), or by reconstruction of the damaged internal carotid artery (using stent, coils or liquid agents). Indirect CCFs may be treated by occlusion of the affected cavernous sinus with coils, liquid agents or a combination of both (Ong C K et al. Journal of Medical Imaging and Radiation Oncology. 2009; 53(3): 291-295; Bhatia K D et al. Journal of Neuro-Ophthalmology. 2009; 29(1): 3-8; Nadarajah M et al. Journal of NeuroInterventional Surgery. 2011; 4(3): e1).
A need exists for an endovascular device capable of treating diseases that require endovascular intervention in a patient suffering from an intracranial aneurysm or a carotid cavernous fistula. The advantages that the described invention possess over comparable devices in treating intracranial aneurysms and carotid cavernous fistulas would be apparent to those skilled in the art. The described invention provides a covered stent device capable of effectively treating such patients by diverting blood flow away from an aneurysm or fistula while allowing blood to flow to critical, healthy adjacent side branching arteries, resulting in blood stasis and thrombus formation inside the aneurysm or fistula.